1. Field of the Invention
This invention relates to a novel process for the preparation of aminoglycoside antibiotics and with novel intermediates for use in such process, and is particularly concerned with a process for the preparation of 1-N-alkyl-substituted-kanamycin derivatives and with selectively N-protected kanamycin derivatives as intermediates for use in the process.
2. Description of the Prior Art
A variety of N-acyl derivatives of kanamycins A and B are reported in the art. Belgian Pat. No. 817,546 describes preparation of N-formyl derivatives of kanamycins A and B formylated on all but the 1-amino group; said compounds being produced by selective hydrolysis of the formyl group from the 1-amino group of fully formylated kanamycins A and B by means of dilute aqueous ammonia.
British Pat. No. 1,464,401 describes 1-N-alkyl derivatives of the kanamycins and Belgian Pat. No. 851,777 broadly discloses preparation of 1-N-(.omega.-amino-2-hydroxyalkyl) derivatives of kanamycins A and B by reductive alkylation of selectively protected kanamycins A and B, including 3,3",6'-tri-N-formyl kanamycin A and 2',3,3", 6'-tetra-N-formyl kanamycin B.
However, none of these references specifically identifies or specifically teaches preparation of 3",6'-di-N-acyl-3-N-formyl kanamycin A derivatives or 2',3",6'-tri-N-acyl-3-N-formyl derivatives of kanamycin B wherein acyl represents C.sub.2-4 alkanoyl or benzoyl. Further, the preparation of such derivatives by selective hydrolysis of the corresponding 3",6'-di-N-acyl-1,3-di-N-formyl kanamycin A or 2',3",6'-tri-N-acyl-1,3-di-N-formyl kanamycin B derivatives is not taught by the art.
Examples of such 1-N-alkyl-substituted kanamycin derivatives are described in British patent specification No. 1,464,401; others are described in Belgian Pat. No. 855,709.